Abstract
Synaptic plasticity underlies the adaptability of the mammalian brain, but has been difficult to study in living animals. Here we imaged the synapses between pre- and postganglionic neurons in the mouse submandibular ganglion in vivo, focusing on the mechanisms that maintain and regulate neurotransmitter receptor density at postsynaptic sites. Normally, synaptic receptor densities were maintained by rapid exchange of receptors with nonsynaptic regions (over minutes) and by continual turnover of cell surface receptors (over hours). However, after ganglion cell axons were crushed, synaptic receptors showed greater lateral mobility and there was a precipitous decline in insertion. These changes led to near-complete loss of synaptic receptors and synaptic depression. Disappearance of postsynaptic spines and presynaptic terminals followed this acute synaptic depression. Therefore, neurotransmitter receptor dynamism associated with rapid changes in synaptic efficacy precedes long-lasting structural changes in synaptic connectivity.
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Acknowledgements
We thank the members of the J. Lichtman and J. Sanes laboratories for thoughtful comments and discussions. We also thank G. Feng (Duke University) and M. Skok for providing antibodies to AChR subunits. C.M.M. was partially supported by the Medical Scientist Training Program grant at Washington University.
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C.M.M. and J.W.L. designed the experiments and wrote the manuscript. C.M.M. and H.K. conducted the imaging experiments. J.C.T. and J.S.C. conducted the electrophysiology experiments.
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Supplementary Text and Figures
Supplementary Figures 1–4 (PDF 357 kb)
Supplementary Movie 1
Endocytosis of BTX labeled AChRs from synaptic receptor clusters. Time-lapse images of an AChR cluster twelve hours after BTX labeling. Some punctate structures moved rapidly; others remained stable and some appeared by budding and then moved away from the cluster. Images were acquired at 5 frames per second. (MOV 2369 kb)
Supplementary Movie 2
Movements of BTX labeled AChRs after endocytosis. Time-lapse images of the cytoplasm of a postganglionic neuron twelve hours after BTX labeling. Intracellular puncta moved rapidly throughout the cytoplasm. Images were acquired at 5 frames per second. (MOV 2075 kb)
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McCann, C., Tapia, J., Kim, H. et al. Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivo. Nat Neurosci 11, 807–815 (2008). https://doi.org/10.1038/nn.2145
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DOI: https://doi.org/10.1038/nn.2145
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